Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence in 2006 is 170 million people and predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin in correspondence with blood glucose levels, maintaining near-constant glucose levels in the body.
Much of the burden of the disease to patients and to health care resources is due to the long-term tissue complications, which affect both small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbA1c) [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining euglycemia by frequent glucose measurements and adjustment of insulin delivery accordingly is of utmost importance.
Conventional insulin pumps deliver rapid-acting insulin 24 hours a day through a catheter placed under the skin. The insulin total daily dose (“TDD”) is typically divided into basal and bolus doses. Basal doses of insulin are delivered continuously over 24 hours to keep blood glucose concentrations within acceptable ranges between meal times and overnight. The amount of insulin continuously delivered over a specific time period may be referred to as the basal rate. In conventional insulin pumps, diurnal basal rates can be pre-programmed or manually changed according to different daily activities. Continuous insulin delivery can be suspended for a predetermined time period to deal with hypoglycemia or with impending hypoglycemia (e.g., when a continuous glucose monitor (“CGM”) alerts of such a predicted situation).
Bolus doses may be delivered during episodes of high blood glucose concentrations and referred to as a “correction bolus” or “CB” or, when delivered before, during or after meals to counteract carbohydrate loads, referred to as a “meal bolus” or “MB.” Conventional parameters used for determining proper bolus doses may include without limitation at least one of the following:                the amount of carbohydrates consumed or to be consumed (“TC”);        the carbohydrate-to-insulin ratio (“CIR”)—the amount of carbohydrates balanced by one unit of insulin measured in grams per unit of insulin. A high or low CIR value indicates that a high or low amount of carbohydrates may be “covered” by one unit of insulin, respectively;        insulin sensitivity (“IS”)—the amount of blood glucose lowered by one unit of insulin measured in milligrams per deciliter (mg/dL) per unit of insulin;        current blood glucose levels (“CBG”) measured in mg/dL;        target blood glucose levels (“TBG”)—a desired blood glucose level measured in mg/dL; and/or        residual insulin (“RI”)—the amount of stored active insulin remaining in the body of a patient after delivery of a bolus dose (also known as “bolus on board” or BOB).        
Additional parameters (e.g., glycemic index) can be also used, and different units can be used, for example “mmol” instead of “mg/dL”.
Conventional insulin pumps may provide bolus dose recommendations based on one or more of the above-listed parameters. For example, an MB dose may be calculated by dividing the amount of carbohydrates (TC) by the CIR. In U.S. Pat. No. 6,936,029 to Mann et al., a recommended bolus dose is calculated based on all of the above-listed parameters as follows:
                    (                  TC          /          CIR                )                    ︸                  “                      Food            ⁢                                                  ⁢            Estimate                    ”                      +                  [                              (                          CBG              -              TBG                        )                    /          IS                ]                    ︸                  “                      Correction            ⁢                                                  ⁢            Estimate                    ”                      -    RI    =      Recommended    ⁢                  ⁢    Bolus    ⁢                  ⁢    Dose  
Some of these parameters are also considered in the bolus dose recommendation feature described in U.S. Patent Application Publication No. US2008/0234663 to Yodfat et al. and International Publication No. WO 2009/133558, the disclosures of which are incorporated herein by reference in their entireties. These publications describe this feature as comprising sets of grids of ranges of carbohydrate amounts and blood glucose levels, wherein each grid may correspond to a different combination of IS, CIR and/or TBG. The publications also note that additional grids may correspond to selected bolus doses and RI values. According to some embodiments in these publications, a final recommended bolus dose may be related to a value substantially similar to the selected bolus dose minus the RI.
IS and CIR values, in particular, are often used to initially set the bolus calculator of many existing pumps or when a user calculates a bolus dose. For Type 1 diabetes patients using rapid-acting insulin, IS values may be determined according to the “2200 to 1600 Rules,” which are commonly used to determine a correction factor that provides guidance as to what CB dose (for example) should be used to reduce high blood glucose concentrations. For example, the 1800 Rule shows how much blood glucose concentrations may drop per unit of rapid-acting insulin (such as insulin aspart (NovoLog®) and/or insulin lispro (Humalog®)) and the 1500 Rule provides a similar indication per unit of regular insulin (e.g., Humulin® R, Novolin® R). The IS value is established by dividing the appropriate Rule by the TDD (e.g., if the TDD is 40 U and the 1800 Rule is applied, the IS value would be 1800 divided by 40, or 45 mg/dL per unit of insulin).
Similarly, Type 1 diabetes patients may determine the CIR using the “450 to 500 Rules,” wherein the 500 Rule is one way to estimate how many grams of carbohydrates will be covered by one unit of rapid-acting insulin (such as aspart (NovoLog®) and/or insulin lispro (Humalog®)). The CIR is established by dividing the appropriate Rule by the TDD (e.g., if the TDD is 40 U and the 450 Rule is used, the CIR would be 450 divided by 40, or about 11 grams per unit of insulin).
Notwithstanding the well-accepted use of the abovementioned “Rules,” drawbacks exist, including without limitation:                inaccuracies in the established IS and CIR due to the limited number of applicable Rules; and        the TDD applied to the Rules is not always known and/or accurate.        
Excessive delivery of insulin doses (i.e., over-dose) or excessive insulin delivery suspensions (DS's) (i.e., under-dose) may imply inadequate insulin regime, such as fault initial insulin delivery programming of basal and/or bolus doses resulting in poor glycemic control (including hypo- and hyper-glycemia). For example, excessive deliveries of CB doses to account for high blood glucose concentrations might stem from an inadequate basal rate and/or MB dose (e.g., from an inappropriately high CIR value). In other examples, excessive DS's to account for low blood glucose concentrations might stem from inappropriately high basal rate and/or MB dose (e.g., from an inappropriately low CIR value).